Association between RCT methodology and disease indication with mineralocorticoid-related toxicity for patients receiving abiraterone acetate for advanced prostate cancer: A meta-analysis of RCTs

Mary E. Hall, Whitney J. Padgett, Zachary Klaassen, Diana E. Magee, Amy N. Luckenbaugh, Aaron A. Laviana, Raj Satkunasivam, Kerry Schaffer, Christopher J.D. Wallis

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

INTRODUCTION: While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration.

METHODS: We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all- and high-grade (grade ≥ 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids.

RESULTS: Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC.

CONCLUSIONS: The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling.

Original languageEnglish (US)
Pages (from-to)e370-e377
JournalClinical Genitourinary Cancer
Volume21
Issue number5
DOIs
StatePublished - Oct 2023

Keywords

  • Abiraterone
  • Antiandrogen
  • Cardiotoxicity
  • Metastatic prostate cancer
  • Prostate Cancer
  • Hypertension
  • Prednisone/therapeutic use
  • Humans
  • Male
  • Treatment Outcome
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects
  • Hypokalemia/chemically induced
  • Randomized Controlled Trials as Topic
  • Mineralocorticoids/therapeutic use
  • Cardiotoxicity/etiology
  • Abiraterone Acetate/adverse effects
  • Prostatic Neoplasms, Castration-Resistant/drug therapy

ASJC Scopus subject areas

  • Urology
  • Oncology

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